The enigmatic biology of rickettsiae: recent advances, open questions and outlook

• Published in: Pathogens and disease 2021-06, Vol.79 (4)
• Main Authors: McGinn, Jon, Lamason, Rebecca L
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - classification; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biology; DNA Transposable Elements; Gene Expression Regulation, Bacterial; Genetics; Genome, Bacterial; Genomes; Host range; Host Specificity - genetics; Host-pathogen interactions; Humans; Intracellular; Life Cycle Stages - genetics; Life cycles; Minireview; Molecular biology; Molecular modelling; Neglected Diseases - microbiology; Neglected Diseases - pathology; Pathogenesis; Pathogens; Protein Interaction Mapping; Questions; Rickettsia; Rickettsia - genetics; Rickettsia - growth & development; Rickettsia - metabolism; Rickettsia - pathogenicity; Rickettsia Infections - microbiology; Rickettsia Infections - pathology; Type IV Secretion Systems - genetics; Type IV Secretion Systems - metabolism
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftab019

ABSTRACT Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host–pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host–pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen. This review highlights the recent advances and insights gained into the unique biology of rickettsiae and key areas for future investigation.